DESCRIPTION (provided by investigator): Maternal transcripts and proteins present in the unfertilized eggs play key roles in directing the earliest developmental programs, as exemplified by a large collection of maternal effect mutants in invertebrates and lower vertebrates. However, very little is known about the function of mammalian maternal gene products. Signaling molecules of the Transforming Growth Factor beta (TGF-2) superfamily are potent regulators of developmental processes and tissue homeostasis. Many components of the TGF-2 family pathways are present in the unfertilized eggs with unknown functions. Conditional oocyte-specific depletion of Smad4, a key transducer of the TGF-2-related signaling, revealed a novel role for this signaling pathway in mammalian preimplantation development. The experiments outlined in this proposal aim to characterize the phenotypic consequences resulted from lacking maternally deposited Smad4 and to elucidate the mechanisms by which Smad4 regulates the process of blastocyst morphogenesis. Detailed immunohistochemistry marker analysis, time-lapse microscopy will be used to analyze the embryonic defects in the absence of maternally supplied Smad4 gene products. In addition, a combination of candidate gene approach and microarray analysis will be employed to identify Smad4-dependent gene responses in preimplantation development. The long term objectives of this project are to elucidate the functions of TGF-2 superfamily signaling in early mammalian development and tissue homeostasis. The proposed studies, designed to uncover mechanisms underlying early mammalian embryonic development, may expand our understanding of congenital diseases and other diseases resulted from disruption of tissue homeostasis. The findings may also provide insights into the biology and behavior of stem cells because of their close connections with preimplantation embryos. The proposed research will take place in an institute with a demonstrated commitment to undergraduate research. The proposal will not only provide valuable research opportunities for students who conduct the experiments, but will also expose a much larger number of students to the excitement of scientific discovery through public presentation of the research data in classes or at conferences. Public Health Relevance: The proposed studies, designed to uncover mechanisms underlying early mammalian embryonic development, may expand our understanding of congenital diseases and other diseases resulted from disruption of tissue homeostasis. The findings may also provide insights into the biology and behavior of stem cells because of their close connections with preimplantation embryos.